Emerging Research in Gastrointestinal Diseases

Abstract

Upper gastrointestinal (GI) ulceration from drugs and stress, as well as inflammatory bowel diseases (IBD) are relatively common GI pathologies which have an appreciable morbidity and mortality. Furthermore, the role of environmental, genetic and nutritional factors in the aetiology of various cancers and other GI disorders emphasizes the importance of research into these and other GI conditions. Each of these pathologies has multiple mechanisms. Recent studies examining the effects of these agents or conditions on the development of acute GI ulceration have highlighted: (1) vascular injury and factors mediating this, among them eicosanoids, endothelins and nitric oxide, (2) leucocyte adhesion, infiltration and activation, (3) neuro-inflammatory reactions, (4) altered production of cytokines, and (5) enteric flora, including Helicobacter pylori. Longer term (chronic) injury involves not only these acute phenomena but also alterations in growth factors and stem cells and the occurrence of complex immuno-inflammatory reactions. In IBD, these alterations are driven by altered T-cell populations and pathological organisms (e.g. Mycobacterium paratuberculosis in Crohn’s disease). An impressive array of strategies have and are being developed to prevent these conditions. Most have focussed on manipulating the mediators, cytokines, growth factors and cells participating in the pathology of these states. For the NSAIDs, procedures have been developed which minimize the occurrence of gastroduodenal mucosal injury (e.g. cyclo-oxygenase-II specific drugs; carboxyl and alkyl nitrite esters; compounds with prostaglandin analogues, micronutrients or other anti-ulcer drugs). Some specific agonists, antagonists or enzymes regulators participating in these reactions have been developed which have impressive actions in animal and human models. However, in some conditions, multivalent drugs may prove more successful, reflecting the multiplicity of factors and cells involved in GI pathologies.